N-disubstituted amino maleimides and succinimides



United States Patent I N-DISUBSTITUTED AMINO MALIfIlMIDES AND SUCCINIMIDES Howard A. Hageman, Southbury, and Winchester L. Hubbard, Woodhridge, Conn., assignors to United States Rubber Company, New York, N.Y., a corporation of New Jersey No Drawing. Original application Feb. 15, 1963, Ser. No. 258,923. Divided and this application Apr. 21, 1965, Ser. No. 449,869

Claims. (Cl. 260-3265) salts, esters and imides of said N-disubstitutedamino amic acids.

The N-disubstitutediamino amic acids are prepared by reacting the selected 1,1-disubstituted hydrazine with the anhydride of the selected dicarboxylic acid. The imides of these acids are prepared by removing water from the acid by means of acetic anhydride.

Illustrative reactions for the formation of N-dimethylaminomaleamic acid and N-dimethylamniomaleimide are as follows:

fl) (H) H /CHa 0 CN-N CH: HC no 0113 ll +H2NN ll H0 H0 The acids may be used as plant growth regulants in the form of the free acids or their equivalent salts, such as the alkali salts, i.e. alkali metal, ammonium or amine (substituted ammonium) salts, e.g. sodium, potassium, ammonium, methyl ammonium, dimethyl ammonium, trimethyl ammonium, ethyl ammonium, ethanol .ammonium, diethanol ammonium, or triethanol ammonium salts, since the salts give equivalent results. The salts may readily be formed directly from the acid and a selected base such as an alkali-metal hydroxide or carbonate, or ammonia, or an amine.

The esters of the N-disubstitutedamino amic acids, such asthe alkyl esters having 1 to 12 carbon atoms in the esterifying radical and the alkenyl esters having 3 to 4 carbon atoms in the esterifying radical may be used as plant growth regulants, e.g. the methyl, ethyl, propyl, butyl, octyl, dodecyl, allyl and methally esters. The esters may be formed by esterifying the selected N-disubstitutedamino amic acid with the selected al- 3,257,414 Patented June 21, 1966 "Ice cohol, or by reacting the selected alcohol with the imide of the selected N-disubstitutedamino amic acid.

The N-disubstitu-tedamino amic acidsand the imides of the present invention may be represented by the general formulae wherein R and R each stand for an alkyl group having 1 to 12 carbon atoms or R and R compositely stand for a (CH --(CH or (-CH CH O group; and R and R each stand for hydrogen, or one of R and R stands for hydrogen and the other stands for a lower alkyl group having 1 to 8 carbon atoms, e.g.

, methyl, butyl, octyl, and R and R each stand for hydrogen, or one of R and R stands for hydrogen and the other stands for one of the following: an alkyl group having 1 to 12 carbon atoms, e.g. methyl, octyl, dodecyl; an alkenyl group having 3 to 12 carbon atoms, e.g. propenyl, tetrapropenyl (C H an aryl group, e.g. phenyl, tolyl, naphthyl; an acyloxy group, e.g. acetoxy; and alkylthio group having 1 to 12 carbon atoms,

e.g. methylthio, hexylthio, dodecylthio; and arylthio radimoiety, and the intermediate two carbon moiety can not be part of an aromatic ring. In the chemicals of the present invention, the intermediate two carbon moiety is part of a functionally aliphatic grouping.

. Examples of chemicals of the present invention are:

N-dimethylaminom-aleamic acid N-diocty-laminomaleamic acid N-didodecylaminomaleamic acid N-(4-morpholinyl)maleamic acid Specific illustrative examples of the preparation of the compounds of the present invention are shown in Examples 1 to below:

EXAMPLE 1 Preparation of N-dimethylaminomaleamic acid A three liter three necked flask containing a solution of 294 g. (3.0 moles) of maleic anhydride in 300 lg. of acetonitrile was immersed in an ice bath. Over one half hour a solution of 180 .g. (3.0 moles) of 1,1-dimethylhydrazine in 100 1g. of acetonitrile was added from a dropping funnel as the reaction mixture was stirred vigorously. During this addition the temperature of the reaction mixture did not exceed 30 C. Near the end of the addition a large amount of a cream colored, crystalline solid precipitated from the solution. After the addition was complete stirring was continued for twenty minutes and then 700 ml. of ether was added to cause further precipitation of the product from solution. Filtration of this reaction mixture gave a filter cake, which after washing with three 100 ml. portions of ether, amounted to 428 g. (90% yield) of N-dimethylaminomaleamic acid of M.P. 121- 124 C.

A sample of this material after one recrystallization from acetone had M.P. 123-125 C.

Analysis-Calculated for C H N O 45.6% C, 6.3% H, 17.7% N; found, 45.9% C, 6.5% H, 17.7% N.

EXAMPLE 2 Preparation of N-'(4-morpholim l)maleamic acid The N-(4 morpholinyl)maleamic acid wasobtained by reacting N-aminomorpholine with maleic anhydride by the procedure of Example 1. It is a colorless crystalline solid of M.P. 172-174 C.

Analysis.--Calculated for C H N O 48.0% C, 6.0% H, 14.0% N; found: 48.3% C, 6.1% H, 13.5% N.

The N-(l-pyrrolidyDmaleamic acid and N-(l-piperidyl)maleamic acid may similarly be prepared from N- aminopyrrolidine and N-aminopiperidine, respectively, and maleic anhydride.

EXAMPLE 3 Preparation of N-dimethylaminomaleimide To 312 g. (2.0 moles) of N-dimethylaminomaleamic acid of M.P. 121-124 C. (prepared as in Example 1) in a 1-liter Erlenmeyer flask was added 255 g. (2.5 moles) of acetic anhydride. Over /2 hour this mixture was gradually warmed to 75 C. on the steam bath. As the temperature reached 65-70 C., all of the solid dissolved to give a clear amber solution. After keeping this solution at 75-80 C. for .4 hour, it was allowed to cool over about 1 hour to 45-50 C.

This solution was then subjected to vacuum distillation employing a short (8-inch) still head. After the acetic acid and acetic anhydride had been removed, the da-rk liquid residue was brought to a temperature of 70 C. under a pressure of 2-3 mm. A yellow-orange liquid distillate amounting to 200 g. was then collected with a still head temperature in the range of 68-84 C. and a pressure of 2-3 mm. As the distillate cooled, it set to a yellow- 4. orange crystalline mass. The residue in the distilling flask consisted of 30-40 g. of a black brittle resin which is readily soluble in water.

The distillate obtained above was then heated successively with several 500 ml. portions of cyclohexaneto 65- 70 C. with agitation. This resulted in a two-phase system in which the cyclohexane layer became a clear gold yellow color. The lower layer consisted of a dark brown viscous oil. After agitation was stopped and the layers had separated cleanly, the hot cyclohexane layer was decanted. After four more similar extractions, the combined cyclohexane solutions (ca. 2.5 liters) were cooled in an ice bath resulting in the precipitation of 133 g. (48% yield) of N-dirnethylaminomaleimide as long bright yellow needles of M.P. 81-83 C. By recrystallizing a sample of this material again from cyclohexane an analytical sample of M.P. 82-83 C. was obtained having the following elemental analysis: calculated for C H N O 51.4% C, 5.7% H, 20.0% N; found, 51.7% C, 5.9% H, 19.5% N.

EXAMPLE 4 Preparation of N-dimethylaminosuccinamic acid To a solution of 50 g. (.50 mole) of succinic anhydride in 150 g. of acetonitrile was added a solution of 30 g. (.50 mole) of 1,1-dimethylhydrazine in 50 g. of acetonitrile. After the exothermic reaction had subsided the mixture was cooled in an ice bath and the precipitate collected by filtration. A yield of 74 g. (92%) of N-dirnethylaminosuccina-micacid as a colorless crystalline solid of M.P. 154-156 C. was obtained. A sample of this material after recrystallization from ethanol gave colorless crystals of M.P. 154-155" C.

EXAMPLE 5 Preparation of N-dimethylaminosuccinimide To 64 g. (.40 mole) of N-dimethylaminosuccinamic acid (prepared as in Example 4) was added g. (.80 mole) of acetic anhydride. After heating this mixture to 100 C. for 15 to 20 minutes, there resulted a clear yellow solution. After keeping at -110 C. for 30 minutes, this solution was allowed to cool slowly (over 30-40 minutes) to 50-55" C. The acetic acid and acetic anhydride were then removed by distillation under a pressure of 5-10 mm. The residual liquid was then maintained' at 80-85 C. for 15 minutes under a pressure of 3-4 mm. There was obtained 53 g. of a clear light amber liquid which set to a crystalline mass after cooling in an ice bath. By recrystallizing this material from ether there was obtained 32 g. of N-dimethylaminosuccinimide as colorless needles of M.P. 5355 C.

EXAMPLE 6 Preparation of ethyl N-dz'methylaminosuccinamate This example illustrates the preparation of an ester from an N-disubstitutedamino amic acid.

Into a mixture of 40 (g. (.25 mole) of N-dimethylaminosuccinamic acid and 300 ml. of absolute ethanol was passed 10 g. of anhydrous HCl. After refluxing this mixture for 2 hours all the solid dissolved to give a clear solution. Over an additional 1 hour, one-half of the ethanol was removed by distillation. After cooling this solution in an ice bath for 1 hour and then adding 100 ml. of ether, the precipitated solid was collected by filtration and washed with ether. There Was obtained 38 g. of the hydrochloride of ethyl N-dimethylaminosuccinamate as colorless crystals of M.P. l25129 C.

A sample of 11.2 g. (.05 mole) of this ester hydrochloride was covered with 200 ml. of ether. After adding 5.0 g. (.50 mole) of triethylamine and vigorously agitating for /2 hour, the mixture was filtered and the filter cake washed with two 50 ml. portions of ether. The filtrate was then reduced to a volume of ml. by distillation. Upon cooling this ether solution in an ice bath mole) of 1,1-dimethylhydrazine.

and subsequently collecting the precipitated solid by filtration, there was obtained 6.2 g. of ethyl N-dimethylaminosuccinamate as colorless crystals of M.P. 7072 C.

EXAMPLE 7 Preparation of n-butyl N-dimethylaminosuccinamate This example illustrates the preparation of an ester from an imide of an N-disubstitutedamino amic acid.

A solution of 14.2 g. (.10 mole) of N-dimethylaminosuccinimide in 74 g. of n-butanol was treated with anhydrous HCl until 3.6 g. (.10 mole) had been absorbed. This slurry was then heated to 105-115 C. for 2 hours giving a clear, colorless solution. After cooling in an ice bath, a white, crystalline solid precipitated. After adding 50 ml. of ether, filtration gave 19.5 g. of colorless crystals of M.P. 102-104 C. This compound is the hydrochloride of n-butyl N-dimethylaminosuccinamate.

A sample of 12.6 g. (.05 mole) of this hydrochloride was covered with 150 ml. of ether. After adding 5.0 g. (.05 mole) of triethylamine, the mixture was vigorously agitated for /2 hour. The solid triethylamine hydrochloride was then removed by filtration and the ether filtrate cooled in an ice bath. Filtration of the precipitated solid gave 4.5 g. of n-butyl N-dimethylaminosuccinamate as colorless crystals of M.P. 4547 C.

EXAMPLE 8 Preparation of N-dimethylamino-alpha-tetrapropenylsuccinamic acid The tetrapropenylsuccinic anhydride employed was obtained from Monsanto Chemical Company and is designated to contain a C H -group in the alpha position. By reacting this anhydride with an equimolar amount to 1,1- dimethylhydrazine in acetonitrile as the reaction medium a clear yellow solution is obtained. After removing the acetonitrile from this solution by distillation under vacuum the N-dimethylamino-alpha-tetrapropenylsuccinamic acid is obtained as a clear yellow viscous liquid.

EXAMPLE 9 Preparation of N-dimethylamino-alpha-acetoxysuccinamic acid To a solution of 15 g. (.10 mole) of alpha-acetoxysuccinic anhydride, of M.P. 56-57 C., in 20 g. of acetonitrile, there was added, in small portions 6.0 g. (.10 During the mixing an ice bath was employed to prevent the temperature of the reaction mixture from exceeding 35 C. After allowing this mixture to stand for one hour, the acetonitrile was removed by distillation under vacuum. By keeping the residue at a temperature of 40-45 C. for two hours under a pressure of 2-3 mm., there was obtained 21 g. of a viscous light brown liquid which partially crystallized after standing several hours.

EXAMPLE Preparation of N-dimethylamino-alpha-phenylthiosuccinimia'e To a solution of 14 g. (.10 mole) of N-dimethylaminoaleimide (prepared as in Example 1) in 20 g. of benzene was added 11 g. (.10 mole) of thiophenol (phenyl mercaptan). After warming this mixture to 60-65 C., a few crystals of benzoyl peroxide were added and the mixture was allowed to stand for 1 /2 hours. After removing the benzene by distillation, the residue was kept at 65-70 C. under a pressure of -2-3 mm. for /2 hour. The residual yellow liquid (24 g.) was dissolved in 70 ml. of warm ethanol. After cooling this solution in an ice bath, the precipitated solid was collected by filtration. There was obtained 17 g. of N-dimethylamino-alpha-phenylthiosuccinimide as colorless crystals M.P. 70-71 C.

The sodium salt of N-dimethylamino-alpha-phenylthiosuccinamic acid may be prepared from the N-dimethylamino-alpha-phenylthiosuccinimide by reaction with sodium hydroxide, and the free acid may be obtained from the sodium salt by treatment witha strong inorganic acid, e.g. hydrochloric acid.

N-dimethylamino-alpha-alkylthiosuccinimides may be prepared similarly to the N-dimethylamino-alpha-phenylthiosuccinimide by reacting the N-dimethylaminomaleimide with the selected alkyl mercaptan.

The chemicals of the present invention may be applied to plants, which term includes various plant parts such as seeds, flowers, fruits, vegetables, roots and foliage in various manners. Seeds may be treated directly with the chemical before planting, or seeds may be treated with the chemical by incorporating the chemical in the soil before or after planting the seeds. The chemicals may be applied to plants in an inert medium as a ,dust in admixture with a powdered solid carrier, such as the various mineral silicates, e.g. mica, talc, pyrophyllite and clays or as an aqueous composition. The chemicals may be applied in admixture with small amounts of surfaceactive wetting agents, which may be anionic, non-ionic, or cationic surface-active agents, generally as aqueous compositions. The chemicals may be dissolved in organic solvents such as acetone, benzene, or kerosene, and the solutions of the chemicals emulsified in water with the aid of surface-active agents. Such surface-active agents are well known and reference is made to US. Patent No. 2,547,724, columns 3 and 4 for detailed examples of the the chemicals of the invention may be admixed with powdered solid carriers, such as mineral silicates, together with a surface-active agent so that a wettable powder may be obtained which may be applied directly to plants, or

- which may be shaken up with water for application to the plants in that form.

The effectiveness of the chemicals of the present invention as plant growth regulants, and particularly as dwarfing agents, is illustrated in the following examples:

EXAMPLE A This example illustrates the treatment of growing plants with the chemicals of the present invention.

Water solutions or dispersions of the chemicals were prepared containing 5000 par-ts per million (p.p.m.) of various chemicals of the invention and a small amount of a surface-active wetting agent (polyoxyethylene sorbitan monolaurate) which is known to be inactive in the testsrun.

Peanut plants in the 2 to 3 leaf stage were sprayed to run off with aqueous compositions prepared as above containing 5000 p.p.m. of

The treated plants and untreated control plants were then placed in a chamber having 100% humidity and a tempera-ture of F. After 24 hours, they were taken out and placed in a greenhouse. The plants were examined two to four weeks after the application of the chemicals. There was a decided dwarfing or shortening of the internodes of the peanut plants treated with the chemicals on comparison with the untreated control plants.

Similar tests to the above on pinto bean plants with application of solutions of 2500, 1250 and 625 p.p.m. of

EXAMPLE B This example illustrates the direct treatment of seeds with the chemicals of the present invention.

Pinto bean seeds were immersed in 100 ml. of aqueous compositions containing 1000 parts per million of the following chemicals prepared similarly to the compositions in Example A:

N-dimethylaminomaleamic acid, N-di-n-dodecylaminomaleamic acid, N-dimethylaminomaleimide, N-(4-morpholinyl)maleamic acid, N-dimethylaminosuccinamic acid,

Ethyl N-dimethylaminosuccinamate, N-dimethylamino-alpha-tetrapropenylsuccinamic acid, N-diimethylamino-alpha-acetoxysuccinamic acid, N-dimethylaminosuccinimide, N-dimethylamino-alpha-p'henylthiosuccinimide.

After four hours, the seeds were removed, washed thoroughly in water for several minutes, and planted in soil contained in four-inch pots. Untreated control seeds were similarly planted. Observations two to four weeks after planting showed decided dwarfing of the plants treated with the chemicals on comparison with the untreated control plants.

EXAMPLE C This example illustrates seed treatment with the chemicals by incorporating the chemicals in the soil.

Two-tenths of a gram of each of the following dry chemicals were mixed uniformly with lb. of dry sand:

N-dimethylarninomaleamic acid, N-dimethylaminomaleamide, N-dimethylamin-osuccinamic acid, N-dimethylaminosuccinimide, and N-dimethylamino-alpha-phenylthiosuccinimide.

The sand and chemical mixtures were then each added to four and a quarter pounds of a 4:1 soil and sand mixture, and were tumbled for five minutes. At the end of this time, the chemicals were uniformly distributed throughout the soil and sand mixture at a rate of one hundred parts of the chemicals per million parts of the soil and sand. The thus treated soil and sand were then placed in 4-inch pots in which pinto bean seeds were planted. Pinto bean seeds were also planted in pots containing untreated con trol soil and sand. Observations after two to four weeks showed definite dwarfing of the plants from seeds that were planted in soil treated with the chemicals of the present invention in comparison with the plants from seeds that were planted in the untreated control soil.

Having thus described our invention, what we claim and desire to protect by Letters Patent is:

1. The cyclic imide of an N-disubstituted amino amic acid in which the disubstituted amino radical is selected from the group consisting of dialkylamino in which each alkyl group has 1-12 carbon atoms, l-pyrrolidyl, l-piperidyl and 4-morpholinyl, and in which the amic acid is selected from the group consisting of maleamic acid, alpha alkylmaleamic acid in which the alkyl group has 1 to 8 carbon atoms, succinamic acid, alpha-alkylsuccinamic acid in which the alkyl group has 1 to 12 carbon atoms, alphahlkenylsuccinamic acid in which the alkenyl group has 3 to 12 carbon atoms, alpha-arylsuccinamic acid in which the aryl group is selected from phenyl, tolyl and naphthyl, alph-a-acetoxysuccinamic acid, alphaalkylthiosuccinamic acid in which the alkyl group has 1 to 12 carbon atoms, and aIpha-arylthiosuccinamic acid in which the aryl group is selected from phenyl, tolyl and naphthyl.

2. N-dialkylaminomaleimide in which each alkyl group has 1 to 12 carbon atoms.

3. N-dimethylaminomaleimide.

4. N-dialkylaminosuccinimide in which each alkyl group has 1 to 12 carbon atoms.

5. N-dimethylaminosuccinimide.

References Cited by the Examiner Curtius, Chemical Abstracts, vol; 10, pages 461-2 (1916).

Horning et al., J. Org. Chem, vol. 20, pages 707-13 (1955).

NICHOLAS S. RIZZO, Primary Examiner. I

. JOSE TOVAR, Assistant Examiner.

,2 73% June 21, 1966 Patent No. Dated H. A. Hageman and W. L. Hubbard Inventor(s) It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Column 2, lines 22 to 29, the structural formula should read:

0 H H C-N-N/ 4 12 R2 R6CH Column 2, lines 30 to 37, the structural formula should read:

Signed and sealed this 8th day of June 1 971 (SEAL) Attest:

EDWARD M.FLETCHER,JR. WILLIAM E. SCHUYLER, JR. Attestlng Officer Commissioner of Patents 

1. THE CYCLIC IMIDE OF AN N-DISUBSTITUTED AMINO AMIC ACID IN WHICH THE DISUBSTITUTED AMINO RADICAL IS SELECTED FROM THE GROUP CONSISTING OF DIALKYLAMINO IN WHICH EACH ALKYL GROUP HAS 1-12 CARBON ATOMS, 1-PYRROLIDYL, 1-PIPERIDYL AND 4-MORPHOLINYL, AND IN WHICH THE AMIC ACID IS SELECTED FROM THE GROUP CONSISTING OF MALEAMIC ACID, ALPHA ALKYLMALEAMIC ACID IN WHICH THE ALKYL GROUP HAS 1 TO 8 CARBON ATOMS, SUCCINAMIC ACID, ALPHA-ALKYLSUCCINAMIC ACID IN WHICH THE ALKYL GROUP HAS 1 TO 12 CARBON ATOMS, ALPHA-ALKENYLSUCCINAMIC ACID IN WHICH THE ALKENYL GROUP HAS 3 TO 12 CARBON ATOMS, ALPHA-ARYLSUCCINAMIC ACID IN WHICH THE ARYL GROUP IS SELECTED FORM PHENYL, TOLYL AND NAPHTHYL, ALPHA-ACETOXYSUCCINAMIC ACID, ALPHAALKYLTHIOSUCCINAMIC ACID IN WHICH THE ALKYL GROUP HAS 1 TO 12 CARBON ATOMS, AND ALPHA-ARYLTHIOSUCCINAMIC ACID IN WHICH THE ARYL GROUP IS SELECTED PHENYL, TOLYL AND NAPHTHYL.
 3. N-DIMETHYLAMINOMALEIMIDE. 